Alzheimer's disease (AD) is a kind of neurodegenerative diseases, and progressive cognitive impairment and memory impairment are the principal characters of AD. Clinically, memory impairment, aphasia, apraxia, agnosia, visuospatial skill impairment, executive dysfunction as well as personality and behavioral changes are the judgment criteria of AD. Currently, there are two kinds of medicaments used to treat AD, acetylcholinesterase inhibitors (such as galantamine) and N-methyl-D-aspartate receptor (NMDA receptor) antagonist (such as memantine), but these drugs are expensive and the side-effects were serious (such as hallucinations, chaotic consciousness, dizziness, headaches and tiredness and the like). Above all these medicaments can only control the patient's condition but cannot reverse it.
Pathogenesis of AD have been investigated for many years by modern medicament, but because of its complex etiology, the pathogenesis of AD is still not clear up to now. β-amyloid protein (Aβ) theory is the mainstream theory of AD, which states that abnormal deposition of Aβ in the brain of patients directly or indirectly affects neurons and glial cells by a series of cascade reactions such as radical reaction, mitochondrial oxidative damage and inflammation, eventually leading to neuronal dysfunction or death, thereby causing memory loss and cognitive impairment, and ultimately resulting in dementia.
Aβ aggregates in the cerebral cortex and hippocampus and subsequently forms senile plaques (SP), which is one of the most major pathological features of AD. Aβ is an important substance leading to AD, which can effectively weaken the structure and function of synap. Therefore, Aβ has become a recognized drug targets in screening medicaments for the prevention or treatment of AD.
Etiology and pathogenesis of AD is complicated, the current medicaments on the market will lead to drug resistance and serious adverse reactions. Traditional Chinese medicaments apply an active multi-component and multi-target approach in the treatment of a serious of diseases, so that Chinese medicaments have obvious advantages on AD treatment.
There may exist close relationship between epilepsy and AD, and Aβ has been identified as the link between these two disorders. In fact, antiepileptic drugs have been involved in preclinical or clinical trial for treating AD. Levetiracetam can suppress neuronal network dysfunction and reverse AD damage and cognitive impairment in mice. Lamotrigine can attenuate deficits in synaptic plasticity and accumulation of amyloid plaques in APP/PS1 transgenic mice and effectively promote their learning memory behavior. Valproic acid can inhibit Aβ generation, neuritic plaque production, ameliorate cognitive performance in AD mice, but it is unlikely to affect patient cognitive function. Carbamazepine and phenytoin can even impair patient cognitive function. Anyhow, repurposing antiepileptic drugs is still available to discover potential anti-AD drug candidates.
News Center of University of California San Francisco reported that antiepileptic drugs named levetiracetam can effectively improve the memory loss caused by Alzheimer, and can reduce damages of the animal model for Alzheimer on Jun. 8, 2012.
The active ingredients of Valeriana Jatamansi Jones, Acorus tatarinowii, and Ramulus Uncariae cum Uncis all have potential effect on Alzheimer's treatment.
So far, there are only five FDA-approved anti-AD drugs on the market. Unfortunately, they can only delay the onset of dementia, and none of them can halt or reverse the disease. These medicaments for treating AD have never met the medical need, and it is urgent to find effective and safe drugs against AD.